Critics rip Cell paper

Improper citation, disregard for antecedent research, and shoddy experimentation - those are just a few of the allegations levied against a recent research paper written by a team of Stanford University scientists.
One of the paper's chief critics, University of Cambridge biologist linkurl:Peter Lawrence,;http://www.mrc-lmb.cam.ac.uk/PAL/ says that the problems with the publication exemplify a broader problem in scientific publishing.
"There's a pressure on scientists to publish in these top j

By Bob Grant | November 25, 2008

Improper citation, disregard for antecedent research, and shoddy experimentation - those are just a few of the allegations levied against a recent research paper written by a team of Stanford University scientists.
One of the paper's chief critics, University of Cambridge biologist linkurl:Peter Lawrence,;http://www.mrc-lmb.cam.ac.uk/PAL/ says that the problems with the publication exemplify a broader problem in scientific publishing.
"There's a pressure on scientists to publish in these top journals," Lawrence told __The Scientist__, "to promote their work as more novel than it really is."
The linkurl:paper;http://www.cell.com/abstract/S0092-8674(08)00680-6 in question, published in a June issue of __Cell__, described a model for understanding the genetic and cellular machinery underlying planar cell polarity (PCP), the cell-to-cell communication that epithelial cells use to align and arrange themselves to function as an organized tissue.
Developmental biologist linkurl:Jeffrey Axelrod,;http://www.stanford.edu/group/axelrodlab/index.shtml the paper's main author, defended the work, writing in an email to __The Scientist__, "our paper (Chen et al. June 2008) underwent Cell's rigorous process of peer-review prior to publication. We stand by our conclusions as stated in the paper, as well as by our use of citations, and I encourage your readers to look at the papers in question, as they speak for themselves."
But Lawrence claims that the Axelrod paper, which identifies a transmembrane protein called Flamingo (also known as starry night or stan) as a key signaling molecule in __Drosophila__ PCP, is largely a rehash of his own group's work, which was linkurl:published;http://www.ncbi.nlm.nih.gov/pubmed/15329345?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum in the journal __Development__ in 2004 and has been cited 35 times, according to ISI. (Axelrod's __Cell__ paper has not yet been cited in any published papers.)
"The complaint is that the main point of the [__Cell__ paper] is what we discovered and provided evidence for four years ago," Lawrence said. "It pretends to be much more novel than it is."
Lawrence wrote in a letter to __Cell__ that the paper was "seriously flawed both scientifically and ethically and in my opinion amounts to a theft of our intellectual property (especially the results and conclusions of our prior paper, Lawrence et al., 2004)." Lawrence's letter was not published in Cell, but he sent it to __The Scientist__. At least four other researchers submitted letters independently - some also obtained by __The Scientist__ - to the journal last July. Some of these also claimed that the Axelrod group's science in constructing a model for PCP was subpar.
"I hope you will agree with me that (i) this paper is a disaster for the field (it will set the community back by several years) and (ii) it is not good for the journal either," wrote linkurl:Marek Mlodzik,;http://www.mountsinai.org/Find%20A%20Faculty/profile.do?id=0000072500001497304492 chair of developmental and regenerative biology at Mount Sinai School of Medicine, in a letter to the editor of __Cell__, Emilie Marcus.
Mlodzik said that the Axelrod paper completely ignores some of his own previous research on PCP; specifically, a 2005 linkurl:paper;http://www.ncbi.nlm.nih.gov/pubmed/16212491?ordinalpos=25&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum that proposed a similar model for PCP. "They should have cited it because of the model," Mlodzik told __The Scientist__.
Mlodzik also takes issue with the science in the __Cell__ paper, citing in his letter to the journal a couple examples where "the authors use wrong data or conceptually flawed experiments to give false credibility to their model."
Lawrence stressed that the scientific problems and lack of proper citation in the __Cell__ paper might be hard to discern by non-experts in the field and that this makes the work even more potentially injurious. "A paper in __Cell__, whatever the quality, will gain citations and eclipse our own discoveries," he said. "We possibly will lose the credit, and we think that is damaging to us."
Mlodzik concurred. In fact, he said he had recently reviewed a research paper on PCP in __Xenopus__ that cited only two __Drosophila__ papers; the Axelrod paper and a review paper. "It just shows the pattern that will emerge from this," he said. The concerns of Lawrence and his colleagues were first brought to light by UK news outlet, linkurl:__Times Higher Education__.;http://www.timeshighereducation.co.uk/story.asp?sectioncode=26&storycode=404296&c=1
Editors at __Cell__ did not respond to an email request for comment in this story. However, the journal's senior scientific editor, Connie Lee, did respond to Lawrence's letter outlining his concerns and requesting to publish a minireview in __Cell__ to set the record straight.
"I can only assure you that the reviewers were experts in PCP and the consensus decision was that the model presented by Chen et al. was thought-provoking, well-supported and provided a sufficient conceptual advance beyond the existing literature," Lee wrote. She declined his request to publish a minireview, instead offered Lawrence the opportunity to post his comments on __Cell__'s website.
Lawrence, with two collaborators, instead wrote a short linkurl:review;http://www.cell.com/current-biology/abstract/S0960-9822(08)01182-2 in an October issue of __Current Biology__, in which they explain some of the problems in Axelrod's Cell paper.
Mlodzik said that in "a perfect world" he'd like to see the Cell paper retracted, but said that for now, making people in the PCP field aware of the problems he perceives in the Axelrod paper will suffice.
Lawrence, however, would like to see action taken to address the issue of scientific scoopsmanship on a broader level. "There should be some kind of scientific ombudsman that people could contact when they feel they've been wronged," he said. "At the moment, there's nothing."
__Update - Nov. 25, 5:00 PM EST: To read the full text of Peter Lawrence's letter, click linkurl:here.;http://images.the-scientist.com/pdfs/articles/TO_CELL.pdf

I concur with a previous post. This issue is very serious and it would be fair to all sides if we could read exactly what each person defends on the matter, rather than presenting a digest of the claims. Obviously, nothing beats reading the original papers to be able to take sides.\n\nIn any case, my limited experience with professional editors of top ranked journals has been a disaster. To publish your paper in these type of journals you end up interacting with a youngster, with no historic vision of the field, with a mediocre personal scientific track record (their major credential for the job is usually a publication in a high impact journal from their postdoctoral period in a powerful laboratory) and infatuated by novelty: instead of editing papers they could be easily marketing iPhones. It is no surprise that many overambitious and unscrupulous scientists end up overselling their stories to these intellectual dwarfs.\n

No wonder the paper in question is being ripped. With protein names like Shoddy, Van Gogh, and Flamingo, how could such work be taken seriously? I can see how Lawrence et al. worry about how people new to the field will think.\n\nOn the other hand, terms like "disaster" and such seem to be a little overblown. It sounds like a bunch of crybabies. All good scientific work is remembered and cited while the poor are relegated to the trash heap.

There are two issues with regard to manuscript review. One is that in some cases well known authors are given a "pass" on their manuscripts because of their stature in the field. One of my undergraduate students left academics after her Ph.D. because, as she said, "I could publish crap in the best journals in the world just because of the lab I am in." The second issue is that less well known investigators, including investigators at smaller schools, can be given harsher reviews than perhaps should be given. "Political Science" is not just in the poly sci department.

Both Mlodzik and Axelrod list each other for sharing reagents and tissues in acknowledgement sections of their recent papers. Chen et al. 2008 (Axelrod's paper) acknowledges Mlodzik for reagents; Wu and Mlodzik, 2008 acknowledge/thank Axelrod (among others) for flies and plasmids. This must be a bitter pill- clearly the researchers were aware of each others' work prior to publication.

The fly field is not exception to controversies. I fully understand Peter Lawrence's concern about somebody republishing data similar to his published work. At another extreme, one fly neurobiologist at a high-profile University has published one incorrect paper in Neuron and another 100% wrong one in Nature. None of these papers have been retracted so far. They do not fool colleagues within the synaptic fields; however, they still mislead readers at large. In comparison, Jeff Axelrod is not that bad. As correctly pointed out by Lawrence, these folks are willingly or under pressure to publish high-profile and flashy stories in top journals. Why? They need these for their promotions and for securing NIH grants! Thus, this malpractice will never stop unless funding agencies such as NIH and NSF set strict rules. I bet that they will reduce the chance if NIH stops their funding.\n\nFlies are wonderful experimental creatures and have served the scientific community well for over 100 years. Do not contaminate this fine culture, please!!

hi\n first of all, in this competitive and commercialized science world, the quality of research is going down. Secondly, because of funding situations, everybody wants to be called their work as ?novel?. to be realistic, then we all are responsible for this kind of situation, we can?t blame each other for the faulty work and these authors are not only the exception!!!!

How to fix this problem? Many Scientists (who are branded as losers for NOT seeking refuge in unethical conduct) scratch their heads all the time to find a cure for this immoral behavior by the so-called SUCCESSFUL scientists. All the scientists are aware that at least in Biology research field - there is no MORALITY left.\n\nThanks to The Scientist to publish information like this. Just go after all these high impact journals and you will easily find how low these biomedical scientists have become just for keeping their jobs and funding alive!!

I am glad to see this general issue come to light. It is far more common than some might think. I have known senior investigators working "hard and smart" in small labs who have been in similar situations and whose protests were either ignored by the journal editors or dismissed with a patronizing response. Some of them became so embittered that they dropped out of science entirely (walking away from tenured faculty positions). \n\nThis is not healthy for the scientific establishment.\n\n

Reality check: the deliberate (or otherwise) disregard for the work of others is rife. What makes this any different to all the other instances is the fact that it has impacted some 'high profile' scientists. Sympathy they may get, but don't ask for special privileges to write a mini-review to be able to correct the record. Wait your turn for the opportunity like everyone else. 'High profile' scientists already get a cushier ride into the big journals and for grant funding than less prominent scientists doing work that is just as good. So either just continue to 'play fair' yourselves and let those that do not get exposed in the natural course of scientific communications OR use your profiles and be proactive and find a way to minimize the deceitful activity for the benefit of everyone. \n\nIn saying this, editors should shoulder some of the responsibility of such actions. A good journal is one that has transparency in its process, independently minded and qualified editors, and should allow post-discussion and debate about the qualities, findings and merits of work that it has published. Isn't this how science is supposed to work? Such mechanisms not only would gain all-important exposure for the journal but also provide valuable feedback as to the choice and quality of what it is publishing. Furthermore, it would provide an indirect assessment of the quality and suitability of the reviewers they choose, and of course the performance of the editors themselves. What better way to achieve their goal to publish the best science than by constant review of their own practices.

This sort of thing happens all the time and most of us know of an example.\n\nOf course one hopes for an "outing" of such abuses by those who claim prior discovery, but it's not likely to happen unless one has the security of an established reputation.

I feel strongly that the review process would be a lot fairer if the authors of papers under review remained anonymous. Reviewers would not be swayed by the fact that the paper was produced by a big lab (or one of their friends).\n\nPerhaps this would go some way towards eliminating shoddy or rehashed data from the field.\n

By way of example that this is a general problem and to widen the discussion I am posting here two abstracts of two papers, the first published in JBC, the second in Nature. \n\nJ Biol Chem. 2006 Mar 10;281(10):6120-3. Epub 2006 Jan 25.\n\n Regulation of fibroblast growth factor-23 signaling by klotho.\n\n Kurosu H, Ogawa Y, Miyoshi M, Yamamoto M, Nandi A, Rosenblatt KP, Baum MG, Schiavi S, Hu MC, Moe OW, Kuro-o M.\n\n Department of Pathology, Pediatrics, and Internal Medicine and Applied Genomics, Genzyme Corporation, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.\n\n The aging suppressor gene Klotho encodes a single-pass transmembrane protein. Klotho-deficient mice exhibit a variety of aging-like phenotypes, many of which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that Klotho and FGF23 may function in a common signal transduction pathway(s), we investigated whether Klotho is involved in FGF signaling. Here we show that Klotho protein directly binds to multiple FGF receptors (FGFRs). The Klotho-FGFR complex binds to FGF23 with higher affinity than FGFR or Klotho alone. In addition, Klotho significantly enhanced the ability of FGF23 to induce phosphorylation of FGF receptor substrate and ERK in various types of cells. Thus, Klotho functions as a cofactor essential for activation of FGF signaling by FGF23.\n\n\n\n\nNature. 2006 Dec 7;444(7120):770-4. Epub 2006 Oct 29. (received by Nature on April 12, 2006) \n\n Klotho converts canonical FGF receptor into a specific receptor for FGF23.\n Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T.\n\n Pharmaceutical Research Laboratories, Kirin Brewery Co., Ltd, 3 Miyahara, Takasaki, Gunma 370-1295, Japan. iurakawa@kirin.co.jp\n\n FGF23 is a unique member of the fibroblast growth factor (FGF) family because it acts as a hormone that derives from bone and regulates kidney functions, whereas most other family members are thought to regulate various cell functions at a local level. The renotropic activity of circulating FGF23 indicates the possible presence of an FGF23-specific receptor in the kidney. Here we show that a previously undescribed receptor conversion by Klotho, a senescence-related molecule, generates the FGF23 receptor. Using a renal homogenate, we found that Klotho binds to FGF23. Forced expression of Klotho enabled the high-affinity binding of FGF23 to the cell surface and restored the ability of a renal cell line to respond to FGF23 treatment. Moreover, FGF23 incompetence was induced by injecting wild-type mice with an anti-Klotho monoclonal antibody. Thus, Klotho is essential for endogenous FGF23 function. Because Klotho alone seemed to be incapable of intracellular signalling, we searched for other components of the FGF23 receptor and found FGFR1(IIIc), which was directly converted by Klotho into the FGF23 receptor. Thus, the concerted action of Klotho and FGFR1(IIIc) reconstitutes the FGF23 receptor. These findings provide insights into the diversity and specificity of interactions between FGF and FGF receptors.

It is interesting to note that 10 of 14 outside comments were posted by "anonymous poster." You cannot have a forceful voice against lack of proper citation in the sciences without standing up and taking credit for your comments.

A blog entry is just one individual's opinions and are provided as 'food for thought' in a discussion. It should not matter whether the author of that entry uses his/her name, or chooses to remain anonymous. Surely, it does not change the value of the comment if it comes from a junior scientist versus a more prominent scientist, so what should it matter. Isn't this the whole point? \nIf blogging was an avenue by which serious change could be facilitated then I would agree with the previous 'post' that authors identify themselves. I would also argue that if effective mechanisms were available to address issues such as those raised in the numerous comments, then I am sure many would jump at the chance to make formal submissions.

Chen, the first author probably did most of the work, but Axelrod, as the so-called "principal investigator", tried to take most credit for it. Now, he must also take most blame, although I'm sure he will try to shift it to Chen.

Axelrod's Paper?\nby anonymous poster\n\n[Comment posted 2008-11-26 16:35:31]\n\nChen, the first author probably did most of the work, but Axelrod, as the so-called "principal investigator", tried to take most credit for it. Now, he must also take most blame, although I'm sure he will try to shift it to Chen. \nxxxxxxxx\n\nHow is it all the time, the first author's fault? Francis Collins blamed it on his Graduate student, Baltimore's scandal - another such story, etc - we can go on and on like this. With all our eyes open, how we always protect the PI, when they are the ones to blame?\n\nThis needs more attention. In 100% of the cases, the PIs encourage this kind of activities and when caught, use their scapegoats - students and postdocs. Funding agencies should be careful in funding these PIs. There should be an awareness among the public not to allow these PIs to continue on this criminal-like behavior.

The real issue herein is several that are pertinent to science in general. The differences between these scientists in this field can be fought on the front lines, side lines, or behind the scene for all I care. \n\nHowever, the first issue raised is the responsibility of the authors of any given body of work to cite the pertinent literature (that also means things from ages ago including pre-1966). More than once at any of the stages of peer-review (editor-in-chief, handling editor, reviewer) have I seen authors who are recognized, the not so recognized, or unrecognized poorly cite the literature. Many times authors, a lot of times from the recognized category, focus on their own research and may leave out the contradicting literature. Is this good science? Absolutely not because of two reasons: 1). It fails to recognize other colleagues efforts, thereby diminishing these efforts [It fails to follow the Golden Rule.] and 2). It fails to offer readers an alternative hypothesis, suggesting a certain level of presumptive intelligence by the offending authors over their less intelligent and obviously wrong colleagues. \n\nThis does not mean that scientists who disagree cannot or should not lay out arguments against another's work in the literature, but rather this is the entire point. We do not grow a field or our understanding of a problem by not having some degree of civil discourse between groups. From this discourse comes more experiments and often a much greater understanding of the problem than originally proposed by any and all of the groups involved in the fracas. \n\nInterestingly, in a class session to our new graduate students, we talked about a lot of these "unwritten rules" and the ethics involved in publishing. The students generated a list of rules for publishing and science misconduct: 1). Don't steal and 2). Don't lie. That pretty much sums up this game, now doesn't it. These students were from 3 continents and all understood the Golden Rule from their own cultures, but amazingly, they were all taught the same points as young children. Now you tell me what is wrong with science publishing.\n\nOne of the students in jest suggested a third rule. This rule was "Don't get caught". Unfortunately, this is an operational approach by too many laboratories. The idea that we can't get caught is often the Achilles heal of many laboratories as illuminated by many of my colleagues' comments herein.\n\nI prefer that authors examine the literature in a meaningful manner. While it is rare for me to do this, more than once in my career have I e-mailed an author with a PDF of "missing citations." It is important to everyone to have their work cited, whether it is that feel good citation by a leading author or for use in the promotion and tenure system. \n\nLastly, the issue of responsibility has been brought up repeatedly by other commentaries herein. I liken this to sports, a good football coach takes responsibility for their teams performance on the field. Behind the scenes the head coach may chastise poor performance or bad decision making by players or other coaches, but publicly, they take the blame. The buck stops here. \n\nAs a PI, there is no way that I cannot take the blame for issues in my lab, no matter how embarrassing such issues might be me. Mistakes happen and poor judgment can occur, none of us are immune to these issues. However, in the end it is my ship, it is my fault. Junior authors cannot be publicly chastised to save the PI's reputation, but rather the PI should step up and take responsibility. Right or wrong, that is the way it needs to be.

I think Eric Murphy's points are excellent and I am wondering if he and others think it would help if journals (as some medical ones do already) invited serious comments on published papers. These would have to be linked closely to the papers themselves, so that anyone who downloaded a paper would find the comments listed conspicuously (Some journals already have blogs, but relevant comments do not appear when you download a paper). They would need to be moderated as the journal would not want to have silly comments, but they should discuss relevant issues of importance, ethical or scientific, raised by the paper in question.\n\nPeople I have discussed this with say there might be too many comments, but I am not so sure, it is hard work to write useful well-researched pieces, and I think people would only bother if they wished to raise something important.\n\nI think top journals should try it as an experiment. In my opinion not only would this practice be educational, I hope it would make journals more interesting to read.

It is very nice to make it a rule that all relevant articles should be cited, but journals them-selves particularly the high impact ones restrict the size of the bibliography section.\n\nShould we consider making supplementary bibliography ? As time passes it becomes an issue as review are cited rather than original paper making recognition of original concept and idea even harder to attribute.

The general issue highlighted in the original post and many of the comments that followed is one of "selective citation." I believe that this example reached the current level of scrutiny because the "complainant" is a well-known scientist and he was willing to raise a public fuss when he felt that his work had been overlooked in a paper published in a prominent journal. \n\nI think it unreasonable that authors be required to cite every prior paper that is relevant to their work. However, failure to cite critical prior work, the complaint raised by Dr. Lawrence, diminishes credit to the original authors and, more significantly, garners excessive credit for the "offending" authors. Whether the "infraction" by the Jacobson lab was deliberate or an honest oversight, I submit that it is not a rare event. \n\nAs a recent example, I cite a paper in Nature, "Oligopotent stem cells are distributed throughout the mammalian ocular surface. Majo F, Rochat A, Nicolas M, Jaoudé GA, Barrandon Y. Nature. 2008 Nov 13;456(7219):250-4" published on line on Oct 1, 2008. While the results described in the paper agree with its title, the authors provide a model that, they say, unifies "our observations with previous results." For the "previous results," they provide a single citation to an important "foundation paper," published in Cell in 1989. This paper made several seminal contributions, among them the localization of label-retaining cells (putative stem cells) to the boundary zone between the corneal and conjunctival epithelia (the corneal "limbus"). However, the authors of the Nature paper overlooked or ignored the results of many intervening papers that directly contradict their model. These studies include in vivo observation of the migration of human corneal epithelial cells and genetic tracer experiments that reveal the source of the corneal progenitor cells in mice. I will not provide all the citations or detail all the findings of these papers, just summarize their findings: they show that basal corneal epithelial cells migrate in a centripetal direction, toward the center of the cornea, not centrifugally, as postulated by Majo, et al. These prior observations don't just disagree with the details of the model put forward in the Nature paper, they demolish it. \n\nWhat went wrong here? 1. Majo, et al. selected an important paper and made it a "straw man." By finding a way to reconcile their data with it, they gave the impression that their model was in agreement with all prior work. They were either unaware of the conflicting studies or chose not to deal with them. Had they done so, they would not have been able to "unify" their results with the bulk of the existing literature. 2. The reviewers of this paper must have been ignorant of the relevant literature. My own work is only peripherally related to corneal stem cells, but I know many papers that are directly relevant to this one. The reviewers must have been unqualified to place the work in the proper context and overly accepting of the authors' assurances. 3. To echo an earlier post, the Nature editors appear to have been unable to identify reviewers with sufficient knowledge of the corneal stem cell literature. This is surprising, as nearly every scientist I know who works in this area would be aware of several studies that contradict the conclusions reached by Majo, et al. \n\nI believe that this problem is a systemic one. Authors practice "selective citation" to inflate the importance of their work and to avoid contrary data that would make their "story" more complicated. Editors, especially some "professional editors" of high profile journals, are not sufficiently knowledgeable to choose reviewers with expertise in the *specific* topic addressed by the paper under review. Reviewers, who may be sticklers for the scientific validity of the experiments in a paper, often overlook the "prior art" in the area addressed by the paper. \n\nWhat can be done? The group with the most power to address this problem is the reviewers... that is US! We can make the Editors' work better by agreeing to review more papers in our area of expertise and by suggesting appropriate reviewers when our schedule forces is to decline an opportunity to review. We should also be sure that we are familiar with the background of a paper; if we are not , a quick Google or PubMed search can help avoid oversights. \n\nAs reviewers, we also need to be more tolerant of papers that openly acknowledge unresolved conflicts in the literature. This is a good thing, not a weakness. Many times, I have been frustrated by a reviewer of one of my papers or grants who uses the same caveats I raised in the Discussion section to beat me up. Reviewers who do this, or insist on "purity" of message, select for authors who conceal conflicts or slant their papers to appear to be the "one true way." The professional culture in some disciplines (this is especially true in epidemiology) is for authors to clearly state the weaknesses of their study design in the Discussion section (for example, "this study employed retrospective chart review. A prospective study would avoid potential biases, etc."). If this practice became the expected norm, it would go a long way toward avoiding the "culture of concealment" that leads to selective citation. As reviewers, we can assure that the authors of papers that sound "too good to be true" are challenged to include a balanced consideration of all the relevant evidence, especially the prior, published work that is the foundation of our profession.

Parts of Peter Lawrence?s work have been duplicated without citation. What would have happened, one might well ask, if the work had not merely been duplicated, but actually copied or plagiarized, with text lifted verbatim and published in a top science journal? \n\nWould Lawrence have managed to persuade the journal to perform a retraction? Would the journal have agreed to publish a review authored by him (to make amends), when such a review would clearly end up casting serious doubts about the quality of the journal?s editorial and reviewing processes, while also damaging its image immensely? \n\nAre journals bereft of the collective ego that human beings possess individually, in ample amounts?\n\nBelow, with a few paragraphs of background information, I describe a personal experience describing what happened to us after some work we published in 2004 was plagiarized and published in a top science journal in 2007. We complained, and there was some (if not altogether satisfactory) remedial action. \n\nThose who wish to see details of what happened - in the form of highlighted versions of the PDFs of the original and plagiarizing papers, and the correspondence with the journal, - can write to me at pg-at-imtech.res.in. \n\nFor those who are not interested in the details, the story below sheds light on at least one possible scenario providing answers to the questions posed above. \n\nIn 2003-2004, we discovered a novel fluorescence in proteins. Considering that ? as everyone knows ? only tryptophan, tyrosine, phenylalanine, certain cofactors (e.g., FAD) and intrinsic chromophores (e.g., GFP) are known to fluoresce in proteins, we were greatly excited. \n\nWe tracked the fluorescence down to loosely held electrons in peptide bonds (the same electrons that are delocalized from their nucleus into the peptide bond?s molecular orbitals, giving peptide bonds their resonant, partially double-bonded character). These already-delocalized electrons appeared to have become further delocalized through hydrogen-bond formation accompanying protein folding (i.e., through the formation of secondary structures such as helices and sheets). In the bargain, in addition to their known absorption in the range of 190-230 nm, the peptide bonds had become amenable to low-energy, long-wavelength ultraviolet excitation (350-400 nm), with consequent visible emission of blue light (400-500 nm). \n\nWhy had no one found it before? Maybe, it was because no one had looked. Anyway, we found that the fluorescence showed variations in the wavelength of maximal emission with changes in secondary structure, consistent with a peptide-based origin for such a novel fluor. Confident that these electrons would be capable of tunneling through networks of peptide bonds and hydrogen bonds, we predicted ? very explicitly - that proteins must conduct electricity ? and therefore end up becoming extremely useful materials in opto-electronics. \n\nWe submitted the paper to many of the top science journals of the world, failed to get them to review our work, and then gradually worked our way down the ladder ? facing much prejudice, and scathing comments, along the way -until finally Arch. Biochem. Biophys. (ABB), to their immense credit, accepted and published the paper. The details are as given below. \n\nShukla, A. et al (2004). A novel UV laser-induced visible blue radiation from proteins : Scattering artefacts or fluorescence transitions of peptide electrons delocalized through hydrogen bonding ? Arch. Biochem. Biophys. 428, 144-153.\n\nSome research groups asked us why we?d published the work in ABB and not in Nature/Science, if indeed what we were reporting was true. Well, what could we say? That we had knocked at the doors of many well-known journals, and failed to get them to send our paper for review? That we had faced what we thought could be an inherent address bias, because few people had heard of the ?Institute of Microbial Technology? where I work? After all, there are enough people who naively believe that these things do not happen. So, we just kept quiet, and went back to doing the other exciting things that we were doing, after publishing our work in ABB. \n\nThen, in 2007, a group from Europe reported in Proc. Natl. Acad. Sci. USA that proteins fluoresce and also conduct electricity through a common underlying phenomenon involving the peptide bond. The details are as given below. \n\nDel Mercato et al. (2007). Charge transport and intrinsic fluorescence in amyloid-like fibrils. Proc Natl Acad Sci U S A. 104, 18019-24. \n \nOur first reaction was pure and innocent delight. Aha?we thought, our discovery was important enough, after all, to have appeared in a top science journal.\n\nRushing to examine whether they?d cited us, we found to our shock and horror that we had not been cited. In hindsight, of course, we realized that if these authors had cited us, then PNAS would probably never have published their paper in the first place. \n\nWhat shocked us more than our not being cited was the fact that the editing and review process at PNAS had worked so shoddily that no one at the journal had bothered to verify the authors? claims of novelty, whereas only two minutes of searching on PUBMED would have revealed to anyone that the results were not original. Much as the top journals claim that they desire to publish only novel work, it is sad but true that this desire is not necessarily backed up by the drive, or the ability, to truly verify either novelty, or importance. \n\nWhat shocked us much more than the shoddiness of the editorial and reviewing processes at PNAS was the fact that the authors had not only re-done every experiment that we?d done (except one) with a different experimental system, they had actually copied language from our paper in ABB, INCLUDING SOME STRETCHES THAT WERE COPIED VERBATIM, especially in the sections that attempted to explain how the fluorescence and the electrical conduction were related. We were dumbfounded at their audacity. What were they thinking, in this age of the internet ?.that they wouldn?t be found out?. Or that no one would listen to a group from the ?Institute of Microbial Technology?? \n\nBut more than all of the above, what shocked us the most of all was this : We are usually asked to give an arm and a leg, in terms of experiments and explanations, for everything that we happen to claim in any of our papers. On the other hand, these guys who?d plagiarized our work had gotten away without either having to explain how they happened to have made the observations that they claimed to have made (i.e., explain why they had looked for a novel fluorescence, or for electrical conduction in proteins, in the first place), or indeed even why they thought that a particular (as it turned out, plagiarized) explanation fitted the data. So much for quality control processes !\n\nAnyway, we complained to PNAS, reporting this to be a case of willful plagiarization, and demanding appropriate action. We did get an apology from the editor-in-chief, and an erratum which appeared five months later; today, I think that we managed to get the erratum because the evidence was water-tight. Others taking stronger, and harsher, positions would probably have managed to get PNAS to retract the paper. The erratum was published in April this year. It hasn?t escaped our notice that a retraction of the offending paper would have eliminated from the literature the only published support of our original observation, till date. What an irony ! Anyway, the details of the erratum are as given below. \n\nDel Mercato et al. (2008). Proc Natl Acad Sci U S A.105,6208.\n\nBefore PNAS published it, we told PNAS that we did not agree with the language of the erratum, since the offending authors agreed to acknowledge only the discovery of the fluorescence, refusing to make any mention of electrical conduction by proteins. PNAS took the side of the offending authors, and published the version of the erratum that the offending authors were agreeable to publishing, without worrying about what we felt about the whole thing. Note ? this is plagiarization that we?re talking about, and not merely lack of citation. Well, what can we say? \n\nFurther, we had also asked PNAS whether we could publish a letter placing developments in proper perspective, but PNAS simply maintained a studied silence on this issue. \n\nWe have now published further findings on this novel protein fluorescence. Once again, after trying several journals, only ABB accepted and published the paper (details below). \n\nGuptasarma, P. (2008). Solution-state characteristics of the ultraviolet A-induced visible fluorescence from proteins. Archives Arch. Biochem. Biophys. 478, 127-129.\n\nThe delight of having this paper published is perfectly balanced by the prospect of its being ignored by future scientists entering the field, just like the last one was. \n\nWho can guarantee that this one also won?t be plagiarized? Who can guarantee that this one will be seen? \n\nSome of the plagiarizing authors are amongst the most well-known nanotechnology groups in the world. One of the authors (Prof. Tamburro) very honorably broke ranks and dissociated himself from the rest of the group when he came to know what had happened (he had been kept out of the loop), but the remaining authors probably remain incensed even today at our audacity in spoiling their party, since we haven?t had the smallest peep of an apology from anyone other than Tamburro. Of course, it is possible that some of the authors remain unaware of all this... who knows? \n\nThe trouble with science is probably the entry of market forces into the scientific workplace; forces that rank fashion, image and impact factor far above content, just like advertising agencies, banks, production units and other market-driven establishments. \n\nIf this is the scientific environment of the future, one might well ask, why should a journal that cares mainly about maintaining its high impact factor sacrifice what it probably holds to be its right (as a business) to choose only those authors who are likely to get cited (and cite each other), while making everyone else walk the plank, especially if running the journal is just like running a business? \n\nAnd who would contend today that journals are not businesses, with all the mergers of publishing houses going on? What do we all expect, with science and business getting mixed up with each other to such a high degree?. like the proverbial tail of the cow, with its dung, to quote an old colloqial saying in this part of the world.\n\nExtrapolating this line of thinking to its logical conclusion, it probably follows that when there are enough scientific 'glitterati' (the page three people of science) on a particular continent who can sustain a highly-ranked journal and keep its impact factor high, naturally scientists from other continents who do not travel to the usual watering holes where such glitterati congregate periodically, will get ignored either subconsciously or consciously, and sometimes with impunity. \n\nSuch things always begin with those who are at the periphery. But everybody forgets that the periphery keeps getting redefined. Nobody is immune to this; not even highly reputed researchers in England?s best universities, it seems. I am shocked. What are things coming to? It is like a variation of the old saying ?When they came to arrest the ?? I thought 'Well, they haven?t come for me'. Now they?ve come for me?. and others who are not directly affected feel about my current plight like I once did about the plight of others?. Hegemony, at all levels, does this. \n\nI am 42 years old. I have had six experiences of this sort already, i.e., papers being deliberately ignored even when they actually have described, proposed, or reported something important (important, at least to me), for the very first time in the world. I have authored only 40 papers (35 as a corresponding author) so far. Those with papers numbering in the hundreds have probably faced many more such instances. \n\nThe practice of science is still the most exciting thing that a human being can do, but I am not sure that young people can survive on the fulfillment that comes from understanding alone, like the middle-aged people of my generation (and preceding generations) have somehow managed to do, in this fast-changing world. \n\nIf science doesn?t get its house in order soon, we may very soon find young people (even those with the right abilities) opting for alternative careers? including, ironically, careers as the very editors who play the journal market because their jobs depend on it. \n\nPurnananda Guptasarma\nInstitute of Microbial Technology, Chandigarh, India \n

For some reason, some of the dashes, apostrophes and single- and double- inverted commas in the text of my posted comment below have been converted into question marks, although everything seemed to be OK when I previewed the posting.\n\nPlease replace the odd (strange?) punctuation marks in some places with the correct ones in your mind (where applicable) as you read the post.

There is nothing necessarily wrong with rehasing results, after all, replication is critical in science. However, not citing the original work is simply unacceptable and unethical, It has become common practice to say "we were the first to show..." even when other previously published the same conclusion. Authors do this to make editors and reviewers think their work is novel when it is not.

A hypothetical situation. Two scientists, one ambitious the other talented working on similar projects. The ambitious scientist does 10 samples to get background data, then reports that they have completed 10,000 samples and writes paper for top journal. Other talented scientist only manages to analyse the 1,000 samples needed to make study statistically relevant by the time the ambitious scientist has published. Ambitious scientist gets tenured position in the faculty over the talented scientist. Once in tenure the ambitious person is now striving for promotion. Meanwhile the talented scientist's grant money runs out and they look for another job after finding it difficult to publish their results which unluckily for them are similar to what the ambitious scientist guessed after 10 samples.\n\nScience prides itself on being meritocratic, with an only the best succeed mentality. Meritocracies however are reknown as selecting for ambition over actual talent. With tenured positions and grant monies limited, ambitious people who are willing to bend the rules will always succeed over those talented individuals who follow the accepted scientific norms. \n\nAs science is made ever more competitive so aberrant behaviours such as cheating and lying will increase to the detriment of the subject. We should not be surprised by it. Cheating and overhyping results can be regarded as a logical and accepted route to success with limited penalties for the few unlucky individuals who are found out and challenged.

I recently was asked to write a review of a field that has not seen a significant clinical advance in 10 years. The journal stipulated that references should be no older than five years unless absolutely necessary. Trouble is, there has been little real progress in the last five. Sure, lots of papers, but little progress. I agree that the number of "eureka" moments (reinventions or repackaging of what was already known some time ago)seem to be on the increase although I witnessed my first case of it in graduate school in a seminar by a "well-respected", aka, powerful cell biologist. Having done some seminal work, ahem, 10 years ago, when it really was a breakthrough, I can't help but wonder what not giving credit to what has gone before really achieves in terms of scientific progress. They should be building on work, not reworking it. Of course if what they are looking for is disdain, they certainly have it from me. One way investigators seem to keep the "cutting edge" sharp is by never actually cutting anything with it. The journals should work to a higher standard.

Suppose you have read everything a specific scientist published, and often read many of his publications repeatedly, because they are very important to yor own work; you have no doubt that he deserves priority for bringing up specific ideas; you definitely wish to give him the priority; but your familiarity with his work is so extensive that you often cannot cite a reference to a specific publication where he raised a specific idea that you consider very important. \n\nWhat are you supposed to do? Checking everything he published just to find the one publication where he raised that idea is practically impossible.\n\nIs it OK to give him priority by merely stating that he was the first one to raise such and such an important idea in print, without providing any specific reference?

Four years ago, I sumbitted a R01 grant to NIH. The reviewers consider the hypothesis is highly significant and idea is highly innovative, but the techniques (approaches) are commonly used, preliminary data are not sufficient and thus risk is high. Then, I published my "insufficient" preliminary data in a non-top journal. One year later, a similar paper was published in PNAS. Three years later when I had "sufficient" preliminary data (my unpublished new preliminary data, which was required by previous reviewers), one of reviewer's comments is that the work has already been done by the applicant and thus the enthusiasm is low. \n\nI was told that most R01 has been done when it was funded. This prompted me to check some funded R01s. R01 is realy notoriously increment research. However, this only apply to the established scientists, who have well public relationship with the scientist in the community, but not to new investigators. Almost all new investigators who are funded by NIH, fist grant is dependent on his/her boss who is well-standing in the circle. Thus, most NIH R01 are incremental except for those "big" shoots who have sufficient funds to do innovative and high risk science. What a science?! Most Amercian Scientists are making a living rather than doing science.

1. Liu, S. 1999. Tracking bacterial growth in liquid media and a new bacterial life model. Science in China (42:644-654,in English entirely). \nAbstract:By increasing viscosity of liquid media above 8.4 centipoise (cp) i.e. 0.084 g?cm-1? s-1, individual growth and family formation of Escherichia coli was continuously observed in real-time for up to 6 h. The observations showed primarily unidirectional growth and reproduction of E. coli and suggested more than one reproduction in the observed portion of E. coli life span. A new bacterial life model is proposed: each bacterium has a stable cell polarity that ultimately transforms into two bacteria of different generations; the life cycle of a bacterium can contain more than one reproduction cycle; and the age of a bacterium should be defined by its experienced chronological time. This new bacterial life model differs from the dominant concepts of bacterial life but complies with all basic life principles based on direct observation of macroorganisms. \n2.Ackermann,M. 2008. Bacteria as a new model system for aging studies: investigations using light microscopy. BioTechnique (44:564-567). \nAbstract:Aging-the decline in an individual's condition over time-is at the center of an active research field in medicine and biology. Some very basic questions have, however, remained unresolved, the most fundamental being: do all organisms age? Or are there organisms that would continue to live forever if not killed by external forces? For a long time it was believed that aging only affected organisms such as animals, plants, and fungi. Bacteria, in contrast, were assumed to be potentially immortal and until recently this assertion remained untested. We used phase-contrast microscopy (on an Olympus BX61) to follow individual bacterial cells over many divisions to prove that some bacteria show a distinction between an aging mother cell and a rejuvenated daughter, and that these bacteria thus age. This indicates that aging is a more fundamental property of organisms than was previously assumed. Bacteria can now be used as very simple model system for investigating why and how organisms age. \nShi V. Liu (SVL8EPA@gmail.com; http://im1.biz; http://blog.sina.com.cn/im1)\n

The mainstream-accepted basic claims for iPSCs are: normal (terminally differentiated adult) somatic cells are directly reprogrammed by some ?inducing? factors and thus de-differentiate to pluripotent stem cells that are indistinguishable from embryonic stem cells (ESCs). Some iPSCs are even ?safe? for regenerative medicine. \nThe "top" journal-rejected different perspectives on iPSCs are: iPSCs obtained so far are more likely originated from rare somatic stem/progenitor cells that have lived from the embryonic into the adult stage of life. The reprogramming may activated their reproduction mechanism and thus increased their proliferation rates. iPSCs are distinguishable from ESCs if looked carefully beside the morphological similarity. No iPSCs made so far are safe because their hyper-proliferation actually reflects their cancer cell nature. \nShi V. Liu (SVL8EPA@gmail.com; http://im1.biz; http://blog.sina.com.cn/im1) \n

After I submitted a proposal to XXX journal requesting a permission to write a Comment or Perspective on its advanced online publication of a discovery that confirms my published discoveries and contradicts a very heavily spun "discovery", the XXX journal sent me the following responses:\nWe will delete your submission without opening and \n"XXX does not wish to consider your inappropriate submissions to the journal, either as formal submissions or as online comments to our material... We have no wish for you to register on our website for any reason. "\nThis is just for your information。 Please restrain yourself from over-reacting to this revelation.\n------Shi V. Liu (SVL8EPA@gmail.com; http://im1.biz; http://blog.sina.com.cn/im1)\n

An editor of a new generation double-open (open access and open review) journal in the first-world had helped a third-world scientist in publishing several controversial papers and saved his career. Then this scientist heard of a hot research topic from this editor who was distributing a condemnation of a citation-problematic high-profile paper in a new top journal because it totally ignored the many publication this editor had on the very same topic and the author as well as that top journal both refused to do anything on that. This third-world scientist wished to do a modeling study on that topic and even asked the editor to give an invitation so that he can visit the first world. \nThen suddenly the editor found that that third-world scientist published a paper in a very top journal but totally ignored the pioneering work of the editor that he knew very well. When confronted with this, he said sorry but did not wish to publish a correction on that journal. The editor of that very top journal received complaint but said that a correction can be published only the author agrees. So the third-world scientist eventually succeeded in scooping a first-world scientist who actually helped him a lot.\nIs this story sad? There are more such stories from this editor.\n------Shi V. Liu (SVL8EPA@gmail.com; http://im1.biz; http://blog.sina.com.cn/im1)\n\n

In 1997, a young scientist was invited to a top research institute to give a formal seminar which presented evidence for a new bacterial/cell life model: one mother cell reproduces one (or more) daughter cell in its life span and the mother cell will retain its older DNA template and distribute the younger DNA template into its daughter cell. This differential DNA strand segregation will not only be a basis for the intrinsic asymmetry - true generation difference - between any paired cells in a reproduction lineage but also a physiological basis for biotic aging and aging associated diseases including cancers. \nA senior scientist approached that junior speaker and said: "your talk touched his heart". However, when that junior speaker was so moved to ask if he can join the lab of the senior scientist the senior scientist said he couldn't accept him because his interest had changed to something else. \nRecently, the junior scientist found that senior scientist published two papers on nonrandom asymmetric DNA/chromosome segregation in a very top journal. But to the greatest disappointment the junior scientist read the senior scientist stated "We are not aware of any study designed specifically to determine the strand distribution of a specific chromosome". \nHow could this happen? \n------Shi V. Liu (SVL8EPA@gmail.com; http://im1.biz; http://blog.sina.com.cn/im1)\n

In 1963, Australians DE Weiss and coworkers* reported high conductivity in iodine-"doped" oxidized polypyrrole blacks. They achieved a conductivity of 1S/cm. Subsequently, deSurville et al** reported high-conductivity in polyanilines. In 1974, Mcginness et al reported a transister-like "switch" composed of a conductive polymer with a high conductivty "ON" state. This device is now in the Smithsonian collection of hstoric electronic devices. See: www.organicsemiconductors.com . \n\n14 years after Weis et als initial report of high conductivity in oxidized iodine-"doped" polypyrolle, Shirakawa et al described the conductive properties of rather similar iodine-doped, oxidized acetylene blacks. Based upon this (re)discovery, they received the 2000 Nobel Prize in Chemistry "For the discovery and development of conductive organic polymers".\n\n*Electronic Conduction in Polymers. III. Electronic Properties of Polypyrrole, BA Bolto, R McNeill and DE Weiss,(1963) Australian Journal of Chemistry, Volume 16 Issue 6, Pages 1090 - 1103\n\n**Electrochem acta 13:1451-1458 (1968). Also see: Historical Background (or there is nothing new under the Sun), Inzelt,G. "Conducting Polymers", (2008),chapter 8,p265-269.\n\n

As both a scientist, reviewer of papers, and as a journal editor I have considerable sympathy for those authors who have been slighted (an understatement) by major journals. I would like to state that some major journals act differently from what has been stated by these authors, but also suggest that the authors did not take the full route to redress. I recently had a complaint from authors that a paragraph from their "under review" paper appeared in a major journal, wondering if that author might have been a referee. Upon checking this out, I found that indeed a referee had apparently used a paragraph describing a new concept almost verbatim. I then referred the complaint both to the apparently errant referee's university ethics committee (University Intellectual Integrity Officer) and to the major journal. The University in question took the issue seriously (though slowly) and after over a year pronounced that plagiary had occurred. The major journal then, because of one plagiarized paragraph, retracted the whole paper, based on the University's verdict. The lessons, (1) universities may take these issues more seriously than journals, and have more tools available to study the issues. Universities have the ability to perform due process. (Journals may fear being sued if they retract an article after their peer reviewers accepted it;) (2) by having more than one body studying the issue, it may be resolved more diligently; (3) (for referees) - you may lose anonymity if you abuse the trust of confidentiality; (4) (for reviewers and editors) beware of authors who profess to be "first". Most papers add incremental findings needed to build a good scientific edifice, and are not major firsts. We must comb the literature carefully before allowing an author to claim a major first.

Some years back I was asked to review a paper submitted as a note to a rather prestigious journal in developmental biology. But to my surprise the paper was almost identical to a publication of mine published four or five years previously. A quick PubMed search would have pulled up my paper immediately. No citations of any of my work in the field were made. That paper never saw the light of day. That was an easy decision, but sometimes it is harder to decide what is accidental and what is unethical.

The present practice of peer review of papers submitted for publication is inadequate and needs to be reformed. \n\nTo do the same thing over and over and expect to get different results is insanity. But, that is basically how the scientific community is dealing (or rather, not dealing) with this issue.\n\nThere is no point in endless hand-wringing over the recurring problem of inadequate refereeing, when there are structural solutions that could address the problem. There should be formal standards for reviewers, if necessary including training and compensation when the review process ought to included time consuming work like re-checking data analysis.\n\nIn this case, several commenters have noted that a literature survey by the reviewers of the offending paper would have turned up omitted citations and prior reports of key findings. This ought to be a standard requirement, in fact the professional staff of the journal should do a key word search as part of due diligence in handling the manuscript, and forward it to reviewers for their comment. \n\nOf course, in this age of open access publication, journals have fewer and fewer resources to devote to concientious redaction. So, unfortunately, problems of poor reviewing will probably get worse, rather than better. Guaranteed, we will read about another example of this in a few months, with the same ineffectual response.